The incidence rate of colectomy for medically refractory ulcerative colitis has declined in parallel with increasing anti‐TNF use: a time‐trend study

Reich, Krista; Chang, Hsiu Ju; Rezaie, Ali; Wang, H.; Goodman, Karen J.; Kaplan, Gilaad G.; Svenson, Larry; Lees, G.J.; Fedorak, Richard N.; Kroeker, Karen I.

doi:10.1111/apt.12873

Cited by 91 publications

(68 citation statements)

References 31 publications

(47 reference statements)

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“…Whether or not this requires a large-scale randomised trial to compare medical and surgical treatment should be debated, particularly as observational studies have shown that treatment with both drugs is associated with a rising colectomy rate as time goes on -as high as 80% at 7 years after treatment with ciclosporin (Table 50) -although the rate appears to be lower, and declining, after infliximab. 122 Long-term follow-up of our trial and cohort patients will be very important to corroborate or refute these findings. We will analyse routinely collected data about readmission, colectomy and mortality over 10 years to look at this.…”

Section: External Validitymentioning

confidence: 76%

Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: pragmatic randomised Trial and economic evaluation (CONSTRUCT)

Williams

Alam

Alrubaiy

et al. 2016

Health Technol Assess

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BackgroundThe efficacy of infliximab and ciclosporin in treating severe ulcerative colitis (UC) is proven, but there has been no comparative evaluation of effectiveness.ObjectiveTo compare the clinical effectiveness and cost-effectiveness of infliximab and ciclosporin in treating steroid-resistant acute severe UC.MethodBetween May 2010 and February 2013 we recruited 270 participants from 52 hospitals in England, Scotland and Wales to an open-label parallel-group, pragmatic randomised trial. Consented patients admitted with severe colitis completed baseline quality-of-life questionnaires before receiving intravenous hydrocortisone. If they failed to respond within about 5 days, and met other inclusion criteria, we invited them to participate and used a web-based adaptive randomisation algorithm to allocate them in equal proportions between 5 mg/kg of intravenous infliximab at 0, 2 and 6 weeks or 2 mg/kg/day of intravenous ciclosporin for 7 days followed by 5.5 mg/kg/day of oral ciclosporin until 12 weeks from randomisation. Further treatment was at the discretion of physicians responsible for clinical management. The primary outcome was quality-adjusted survival (QAS): the area under the curve (AUC) of scores derived from Crohn’s and Ulcerative Colitis Questionnaires completed by participants at 3 and 6 months, and then 6-monthly over 1–3 years, more frequently after surgery. Secondary outcomes collected simultaneously included European Quality of Life-5 Dimensions (EQ-5D) scores and NHS resource use to estimate cost-effectiveness. Blinding was possible only for data analysts. We interviewed 20 trial participants and 23 participating professionals. Funded data collection finished in March 2014. Most participants consented to complete annual questionnaires and for us to analyse their routinely collected health data over 10 years.ResultsThe 135 participants in each group were well matched at baseline. In 121 participants analysed in each group, we found no significant difference between infliximab and ciclosporin in QAS [mean difference in AUC/day 0.0297 favouring ciclosporin, 95% confidence interval (CI) –0.0088 to 0.0682;p = 0.129]; EQ-5D scores (quality-adjusted life-year mean difference 0.021 favouring ciclosporin, 95% CI –0.032 to 0.096;p = 0.350); Short Form questionnaire-6 Dimensions scores (mean difference 0.0051 favouring ciclosporin, 95% CI –0.0250 to 0.0353;p = 0.737). There was no statistically significant difference in colectomy rates [odds ratio (OR) 1.350 favouring infliximab, 95% CI 0.832 to 2.188;p = 0.223]; numbers of serious adverse reactions (event ratio = 0.938 favouring ciclosporin, 95% CI 0.590 to 1.493;p = 0.788); participants with serious adverse reactions (OR 0.660 favouring ciclosporin, 95% CI 0.282 to 1.546;p = 0.338); numbers of serious adverse events (event ratio 1.075 favouring infliximab, 95% CI 0.603 to 1.917;p = 0.807); participants with serious adverse events (OR 0.999 favouring infliximab, 95% CI 0.473 to 2.114;p = 0.998); deaths (all three who died received infliximab;p = 0.247) or concomitant use of immunosuppressants. The lower cost of ciclosporin led to lower total NHS costs (mean difference –£5632, 95% CI –£8305 to –£2773;p < 0.001). Interviews highlighted the debilitating effect of UC; participants were more positive about infliximab than ciclosporin. Professionals reported advantages and disadvantages with both drugs, but nurses disliked the intravenous ciclosporin.ConclusionsTotal cost to the NHS was considerably higher for infliximab than ciclosporin. Nevertheless, there was no significant difference between the two drugs in clinical effectiveness, colectomy rates, incidence of SAEs or reactions, or mortality, when measured 1–3 years post treatment. To assess long-term outcome participants will be followed up for 10 years post randomisation, using questionnaires and routinely collected data. Further studies will be needed to evaluate the efficacy and effectiveness of new anti-tumour necrosis factor drugs and formulations of ciclosporin.Trial registrationCurrent Controlled Trials ISRCTN22663589.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 44. See the NIHR Journals Library website for further project information.

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Section: External Validitymentioning

confidence: 76%

Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: pragmatic randomised Trial and economic evaluation (CONSTRUCT)

Williams

Alam

Alrubaiy

et al. 2016

Health Technol Assess

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“…This was true for both elective (-14.9%) and urgent (-18.6%) procedures. There was no difference in the use of corticosteroids, aminosalicylates and thiopurines during the study period [17] . In a retrospective study using 4 province-wide population-based databases in British Columbia, Canada colectomy rate during preinfliximab (2003)(2004)(2005)(2006) and postinfliximab (2007-2010) period was compared [18] .…”

Section: Impact Of Immunomodulatorsmentioning

confidence: 88%

“…Only patients using thiopurines for more than 12 months (probably responders to thiopurines) had a decreased risk of colectomy compared to those with shorter treatment duration (HR 0.29, 95% CI 0.21-0.40) [12] . The impact of anti-TNFα therapy on colectomy rate during the period 1998-2011 was assessed in a retrospective hospital-based study from Canada [17] . After the introduction of biologic therapy in 2005, a decline in total colectomy incidence by 16.1% was observed.…”

Section: Impact Of Immunomodulatorsmentioning

confidence: 99%

What Can We Learn from Epidemiological Studies in Inflammatory Bowel Disease?

Ďuricová

2017

Dig Dis

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Background: Population-based studies represent the whole spectrum of patient population and should represent the mainstay when evaluating patients' prognosis. A high number of CD patients need surgical intervention during the disease course. The disease course of inflammatory bowel diseases, including ulcerative colitis (UC) and Crohn's disease (CD), is quite varied and still quite unpredictable. Key Messages: According to earlier studies, up to 60% of patients undergo at least one operation after 10 years of CD duration. Newer cohorts report lower cumulative probability of surgery of approximately 40% after 10 years. The colectomy rate in UC is approximately 10% after 10 years from diagnosis with a geographic difference. Similarly to CD, the colectomy rate seems to decrease over time. There is some evidence that the increasing use of immunosuppressive and/or biological therapy might have been responsible for this favourable trend. However, other factors may have an impact on decreasing surgical trend over time. The relative risk (RR) of colorectal cancer (CRC) in UC is approximately doubled compared to background population. However, the absolute risk in general is relatively low between 1.1 and 5.3% after 20 years of disease duration. Furthermore, a decreasing trend in the incidence of CRC has been reported in recent studies. Importantly, several factors such as disease extent, activity, age at UC onset, and so on may increase/modify an individual risk. Similar to UC, CD patients have approximately 2 times higher RR of cancer compared to background population. The risk is higher for colon than for rectum cancer and present only in CD patients with colonic involvement. Conclusions: The surgery rate in CD has decreased over the time period. The evidence on colectomy rate in UC is less conclusive. The RR of CRC in UC and CD is approximately doubled compared to that of the background population, but it seems to be decreasing in more recent cohorts.

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“…From 2005 to 2011, following the approval and increasing use of anti-TNF therapy, the total colectomy incidence rate decreased by 16.1% (95% CI, 221.32% to 210.54%) every year to 0.9 per 100 ulcerative colitis patients in 2011. 22 In contrast, a recent population-based cohort from Olmsted County reported a 18.9% colectomy rate at 10-years 23 ; in addition, patients diagnosed in the period of 2000 to 2004 were nearly 4 times more likely to require colectomy compared with patients diagnosed in 1970s. A recent systematic review and meta-analysis of population-based studies has demonstrated that the risk of surgery in 1, 5, and 10 years after diagnosis of UC is 4.9 (95% CI, 3.8%-6.3%), 11.6% (95% CI, 9.3%-14.4%), and 15.6% (95% CI, 12.5%-19.6%), respectively.…”

Section: Discussionmentioning

confidence: 91%